16p13.11 microduplication syndrome

Summary

16p13.11 microduplication syndrome (MONDO:0016837) is a disease with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 5
• Phenotypes (HPO): 19

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		162	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0001161	Hand polydactyly	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0002463	Language impairment	Frequent (30-79%)
HP:0007018	Attention deficit hyperactivity disorder	Frequent (30-79%)
HP:0001382	Joint hypermobility	Frequent (30-79%)
HP:0000268	Dolichocephaly	Occasional (5-29%)
HP:0000717	Autism	Occasional (5-29%)
HP:0000718	Aggressive behavior	Occasional (5-29%)
HP:0000767	Pectus excavatum	Occasional (5-29%)
HP:0001166	Arachnodactyly	Occasional (5-29%)
HP:0001363	Craniosynostosis	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001636	Tetralogy of Fallot	Occasional (5-29%)
HP:0001669	Transposition of the great arteries	Occasional (5-29%)
HP:0001680	Coarctation of aorta	Occasional (5-29%)
HP:0001763	Pes planus	Occasional (5-29%)
HP:0100753	Schizophrenia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	16p13.11 microduplication syndrome
Mondo ID	MONDO:0016837
Orphanet	261243
SNOMED CT	719578005
UMLS	C4304595
MedGen	930264
GARD	0020775
Is cancer (heuristic)	no

Also known as: 16p13.11 recurrent microduplication (neurocognitive disorder susceptibility locus) · dup(16)(p13.11) · trisomy 16p13.11

Data availability: 5 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › chromosomal disorder › syndrome caused by partial chromosomal duplication › partial duplication of chromosome 16 › partial duplication of the short arm of chromosome 16 › 16p13.11 microduplication syndrome

Related subtypes (5): congenital cataracts-facial dysmorphism-neuropathy syndrome, chromosome 16p13.3 duplication syndrome, chromosome 16p11.2 duplication syndrome, 16p11.2p12.2 microduplication syndrome, 16p12.1p12.3 triplication syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

4 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2580319	GRCh37/hg19 16p13.11(chr16:15125542-16388672)x3	ABCC1	Pathogenic	criteria provided, single submitter
1703614	GRCh37/hg19 16p13.11(chr16:14892880-16544222)	ABCC1	Likely pathogenic	no assertion criteria provided
1703615	GRCh37/hg19 16p13.11(chr16:14892880-16533890)	ABCC1	Likely pathogenic	no assertion criteria provided
3235935	GRCh38/hg38 16p13.12-12.3(chr16:15034129-16187150)	CEP20	Likely pathogenic	criteria provided, single submitter
3235906	GRCh38/hg38 16p13.12-13.11(chr16:15032610-16203929)	NOMO3	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCC1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NOMO3	HGNC:25242	ENSG00000103226	P69849	BOS complex subunit NOMO3	clinvar
CEP20	HGNC:26435	ENSG00000133393	Q96NB1	Centrosomal protein 20	clinvar
ABCC1	HGNC:51	ENSG00000103222	P33527	Multidrug resistance-associated protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NOMO3	BOS complex subunit NOMO3	Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes.
CEP20	Centrosomal protein 20	Involved in the biogenesis of cilia.
ABCC1	Multidrug resistance-associated protein 1	Mediates export of organic anions and drugs from the cytoplasm.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transporter	1	25.9×	0.114
Antibody/Immunoglobulin	1	9.7×	0.149
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NOMO3	Antibody/Immunoglobulin	yes		CarboxyPept-like_regulatory, Ig-like_fold, Carb-bd-like_fold
CEP20	Other/Unknown	no		LisH, FOP_dimerisation-dom_N
ABCC1	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, MRP

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	1
corpus callosum	1
pancreas	1
islet of Langerhans	1
muscle of leg	1
skeletal muscle tissue	1
lower esophagus	1
lower esophagus mucosa	1
lower esophagus muscularis layer	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NOMO3	134	tissue_specific	marker	body of pancreas, pancreas, corpus callosum
CEP20	143	ubiquitous	marker	islet of Langerhans, skeletal muscle tissue, muscle of leg
ABCC1	134	ubiquitous	marker	lower esophagus mucosa, lower esophagus, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCC1	3,018
CEP20	772
NOMO3	428

Intra-cohort edges

A	B	Sources
CEP20	NOMO3	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCC1	P33527	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NOMO3	P69849	80.74
CEP20	Q96NB1	73.95

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 3 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Metabolism of porphyrins	1	1427.5×	0.006	ABCC1
Transport of RCbl within the body	1	1427.5×	0.006	ABCC1
NFE2L2 regulating MDR associated enzymes	1	1427.5×	0.006	ABCC1
Heme degradation	1	815.7×	0.006	ABCC1
Cobalamin (Cbl, vitamin B12) transport and metabolism	1	634.4×	0.006	ABCC1
Synthesis of Leukotrienes (LT) and Eoxins (EX)	1	571.0×	0.006	ABCC1
Arachidonate metabolism	1	571.0×	0.006	ABCC1
Paracetamol ADME	1	423.0×	0.007	ABCC1
Nuclear events mediated by NFE2L2	1	335.9×	0.008	ABCC1
Sphingolipid de novo biosynthesis	1	285.5×	0.008	ABCC1
Drug ADME	1	228.4×	0.010	ABCC1
Cytoprotection by HMOX1	1	184.2×	0.010	ABCC1
Metabolism of water-soluble vitamins and cofactors	1	181.3×	0.010	ABCC1
Sphingolipid metabolism	1	167.9×	0.010	ABCC1
Cellular response to chemical stress	1	142.8×	0.011	ABCC1
Fatty acid metabolism	1	131.3×	0.011	ABCC1
ABC-family protein mediated transport	1	121.5×	0.011	ABCC1
KEAP1-NFE2L2 pathway	1	120.2×	0.011	ABCC1
Metabolism of vitamins and cofactors	1	116.5×	0.011	ABCC1
Cellular responses to stress	1	36.8×	0.033	ABCC1
Metabolism of lipids	1	31.6×	0.035	ABCC1
Cellular responses to stimuli	1	31.5×	0.035	ABCC1
Transport of small molecules	1	25.1×	0.041	ABCC1
Metabolism	1	11.6×	0.086	ABCC1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
antigen processing and presentation of lipid antigen via MHC class Ib	1	5617.3×	0.003	ABCC1
cyclic nucleotide transport	1	5617.3×	0.003	ABCC1
sphingolipid translocation	1	5617.3×	0.003	ABCC1
intracellular nitrogen homeostasis	1	5617.3×	0.003	ABCC1
pigment accumulation	1	2808.7×	0.004	ABCC1
granuloma formation	1	1872.4×	0.005	ABCC1
glutathione transmembrane transport	1	1404.3×	0.005	ABCC1
neural tissue regeneration	1	1404.3×	0.005	ABCC1
negative regulation of nodal signaling pathway	1	1404.3×	0.005	NOMO3
glucocorticoid metabolic process	1	936.2×	0.005	ABCC1
amygdala development	1	936.2×	0.005	ABCC1
NK T cell activation	1	936.2×	0.005	ABCC1
carboxylic acid transmembrane transport	1	936.2×	0.005	ABCC1
xenobiotic transport across blood-brain barrier	1	936.2×	0.005	ABCC1
leukotriene transport	1	802.5×	0.005	ABCC1
lymphocyte migration	1	802.5×	0.005	ABCC1
determination of left/right asymmetry in lateral mesoderm	1	624.1×	0.005	NOMO3
cobalamin transport	1	624.1×	0.005	ABCC1
response to fluid shear stress	1	624.1×	0.005	ABCC1
multi-pass transmembrane protein insertion into ER membrane	1	624.1×	0.005	NOMO3
export across plasma membrane	1	561.7×	0.005	ABCC1
heme catabolic process	1	510.7×	0.005	ABCC1
amyloid-beta metabolic process	1	510.7×	0.005	ABCC1
hydrogen peroxide biosynthetic process	1	468.1×	0.005	ABCC1
endothelium development	1	432.1×	0.005	ABCC1
leukotriene metabolic process	1	432.1×	0.005	ABCC1
leukotriene biosynthetic process	1	432.1×	0.005	ABCC1
microtubule anchoring	1	432.1×	0.005	CEP20
endothelial cell apoptotic process	1	432.1×	0.005	ABCC1
transepithelial transport	1	401.2×	0.005	ABCC1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ABCC1	RIMONABANT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCC1	23	4
NOMO3	0	0
CEP20	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIMONABANT	4	ABCC1
VINBLASTINE	4	ABCC1
CYCLOSPORINE	4	ABCC1
DAUNORUBICIN	4	ABCC1
ETRAVIRINE	4	ABCC1
BENZBROMARONE	4	ABCC1
ESTRONE SULFURIC ACID	4	ABCC1
DOXORUBICIN	4	ABCC1
MITOXANTRONE	4	ABCC1
INDOMETHACIN	4	ABCC1
IVERMECTIN	4	ABCC1
VERAPAMIL	4	ABCC1
VINCRISTINE	4	ABCC1
VALSPODAR	3	ABCC1
TARIQUIDAR	3	ABCC1
QUERCETIN	3	ABCC1
DEXVERAPAMIL	2	ABCC1
VEDROPREVIR	2	ABCC1
VERLUKAST	2	ABCC1
BIRICODAR	2	ABCC1
CLESACOSTAT	2	ABCC1
BMS-754807	2	ABCC1
KAEMPFEROL	1	ABCC1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ABCC1	459	Binding:270, Functional:166, ADMET:23

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABCC1	7.6.2.2, 7.6.2.3	ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ABCC1	459

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

23 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
RIMONABANT	4	ABCC1
VINBLASTINE	4	ABCC1
CYCLOSPORINE	4	ABCC1
DAUNORUBICIN	4	ABCC1
ETRAVIRINE	4	ABCC1
BENZBROMARONE	4	ABCC1
ESTRONE SULFURIC ACID	4	ABCC1
DOXORUBICIN	4	ABCC1
MITOXANTRONE	4	ABCC1
INDOMETHACIN	4	ABCC1
IVERMECTIN	4	ABCC1
VERAPAMIL	4	ABCC1
VINCRISTINE	4	ABCC1
VALSPODAR	3	ABCC1
TARIQUIDAR	3	ABCC1
QUERCETIN	3	ABCC1
DEXVERAPAMIL	2	ABCC1
VEDROPREVIR	2	ABCC1
VERLUKAST	2	ABCC1
BIRICODAR	2	ABCC1
CLESACOSTAT	2	ABCC1
BMS-754807	2	ABCC1
KAEMPFEROL	1	ABCC1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ABCC1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	NOMO3
E	Difficult family or no structure, no drug	1	CEP20

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
NOMO3	0	—
CEP20	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.